Role of fibroblast growth factor 23 in health and in chronic kidney disease

PURPOSE OF REVIEWThis review summarizes the molecular properties and biological roles of a new phosphaturic factor, fibroblast growth factor 23 (FGF23). Significant roles of FGF23 are discussed, especially in terms of its effects on the kidney, the main target organ. RECENT FINDINGSFGF 23 is a recently discovered phosphaturic factor. Several animal experiments including overexpression or ablation of the FGF23 gene have recently revealed the significant effects of this factor on phosphate excretion and on vitamin D synthesis in the kidney. Although FGF23 was originally identified as a factor responsible for several hypophosphatemic disorders, recent data indicate its role in the physiological regulation of phosphate homeostasis. In chronic kidney disease, FGF23 plays a crucial role in the pathogenesis of secondary hyperparathyroidism. Effects of FGF23 on other organs including bone and intestine remain to be elucidated. SUMMARYFGF23 is a physiological regulator of phosphate homeostasis. Excessive activity of FGF23 with normal renal function results in hypophosphatemia, low 1,25-dihydroxyvitamin D levels, and rickets/osteomalacia. By contrast, excessive FGF23 activity suppresses 1,25-dihydroxyvitamin D synthesis, but may not be sufficient to excrete the phosphate load appropriately with deteriorating renal function, both of which contribute to the development of hyperparathyroidism.